Organ differential-growth models indicate that control of organ size occurs at the level of the entire tissue volume; that is, no single factor such as cell size or the number of cells within the organ is responsible for size of the organ. How organ mass is sensed is not known. The system of control is complex, as well as robust and stable towards changes in individual factors (Desplan, C. and Lecuit, T., Nature, 422, 123-124, 2003).
An integrated picture has yet to emerge of the totality of controls on tissue and internal organ size, either during development or adulthood. Known molecular influences tend to be upregulatory (i.e. stimulatory, such as growth hormone and the sex steroids), stimulatory or inhibitory depending on the situation (e.g. TGFβ), or specifically inhibitory (e.g. locally produced myostatin on muscle, or Noggin, which counters the growth factor bone morphogenetic protein 7), rather than generally inhibitory, as in the present invention. Further examples of intercellular signalling molecules which might play a role in the control of organ size and form include classical hormones such as insulin and prolactin; effectors such as IGF1 and 2, TGFα, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF); and morphogens involved in differentiation and patterning such as Wnt, Notch and Hedgehogs.
Circulating hormone levels can control tissue and organ size directly, as in the case of upregulation of the size of the prostate gland by androgens. Some agents influence growth indirectly on a ‘global’ scale in the body, by exerting an effect on central hormonal growth control in the hypothalamus and pituitary. Estrogen, while also having local effects, is an example of a hormone that exerts control on growth and size in this way. Of particular interest is when the decision point is reached to reproduce rather than continue growing.
In WO 00/32208 impure preparations of sheep ovarian venous plasma were used to show that fractions collected in the 10-30 kDa nominal molecular weight range contained a material which reduced organ mass in adult rats. This was the first time it was shown that a general inhibitor of organ mass existed. The unknown active entity in the material was named ‘micrin’. That document provided no information on the chemical nature of micrin.
An object of the present invention is to overcome deficiencies of the prior art. This and other objects will become apparent from the following description.